叶酸受体靶向星形聚己内酯纳米胶束的制备和性质

Preparation and characterization of folate receptor-mediated targeting star-shaped poly (epsilon-caprolactone)

背景：近年来,在药物载体材料领域,两亲性星形聚合物的自组装胶束化引起了人们的关注。叶酸官能团作为肿瘤靶向基团被越来越多地引入药物载体,显示出了良好的靶向效应。目的：制备一种新型的末端接叶酸的星形聚己内酯（StarPCL-FA）材料胶束,并对其性质进行表征,为其在控释给药系统中的应用提供基本依据。方法：以四氢呋喃为溶剂,采用溶剂挥发法制备StarPCL-FA的胶束溶液。动态光散射粒度仪、透射电子显微镜测量胶束的粒径和表面形貌;考察稀释对胶束粒径的影响及水中胶束粒径随时间的变化情况;采用芘荧光探针技术测定共聚物的临界胶束质量浓度;用β-胡萝卜素作为模型药物对胶束载药量进行研究。结果与结论：成功制备了星形聚合物StarPCL-FA胶束,胶束的粒径为纳米级,临界胶束质量浓度值较低,胶束对稀释较为稳定,且能在37℃的水中较长时间稳定存在,但随着时间延长,出现粒径轻微增大现象,说明胶束在水中能够稳定存在且对稀释的稳定性较好,这对于其在注入人体时避免药物的暴释具有重要意义。另外用β-胡萝卜素作为模型药物对胶束载药量研究表明其载药量为3.0%~4.0%。说明胶束对β-胡萝卜素有包载能力,但其载药能力还有待提高。

BACKGROUND：Recently,the interest in micellization of amphiphilic star-shaped polymer has exponentially increased in the field of drug delivery.Folic acid（FA）has been introduced into drug delivery system as tumor targeting group and shows excellent targeting effect.OBJECTIVE：To prepare a new class of folic acid end functionalized star-shaped poly（ε-caprolactone）（StarPCL-FA）micelle,and investigate its property in order to draw a basic line for its application in drug delivery system.METHODS：Micelles were prepared by means of solvent evaporation,using tetrahydrofuran（THF）as organic phase.Size and morphology of micelle were detected using dynamic light scattering device and transmission electron microscope;the effect of dilution on the micelle size with time prolonging was measured;critical micellization concentration（CMC）was detected using pyrene fluorescence probe spectrometry;drug loading efficiency and encapsulation efficiency were measured based on β-carotene.RESULTS AND CONCLUSION：Polymer micelle was successfully prepared with StarPCL-FA,the size of resulting micelle was nano-scale,CMC was relatively low,and the micelle was stable with dilution and existed for a long time in pure water.However,a slightly increase of the size was observed with time prolonging.The micelle prepared was stable in water with time and with dilution,which was essential for drug delivery because the burst-like release of drug from micelles could be avoided when injected into blood stream.In addition,the drug loading efficiency with β-carotene as model drug was measured about 3%-4 %.The micelle had an ability of loading β-carotene;however the loading efficiency could be further improved.